Dystrophin, the protein product of the Duchenne/Becker muscular dystrophy locus, is normally present in muscle tissues and the brain. Approximately one third of patients exhibit a mild degree of mental retardation which is presumably caused by abnormalities of dystrophin. We propose to accurately localize dystrophin within the nervous system and determine what role it might play in normal cognitive function. Attempts will be made to isolate as cDNA clones those proteins which interact with dystrophin in neurons, and experiments will be designed to understand the nature of this interaction. Patients will be sought who have abnormalities of dystrophin expressed in the brain, but normal expression of dystrophin in muscle. Clinical findings in such patients may reveal insights into normal neuronal development and how it is altered in mental retardation. Finally, we propose to characterize the novel shorter dystrophin transcripts which are also expressed in normal brain and may have a role in mental development.